气候变化领域集成服务门户(CCPortal): HIV envelope tail truncation confers resistance to SERINC5 restriction

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DOI	10.1073/pnas.2101450118
	HIV envelope tail truncation confers resistance to SERINC5 restriction
	Haider T.; Snetkov X.; Jolly C.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:21
英文摘要	SERINC5 is a potent lentiviral restriction factor that gets incorporated into nascent virions and inhibits viral fusion and infectivity. The envelope glycoprotein (Env) is a key determinant for SERINC restriction, but many aspects of this relationship remain incompletely understood, and the mechanism of SERINC5 restriction remains unresolved. Here, we have used mutants of HIV-1 and HIV-2 to show that truncation of the Env cytoplasmic tail (ΔCT) confers complete resistance of both viruses to SERINC5 and SERINC3 restriction. Critically, fusion of HIV-1 ΔCT virus was not inhibited by SERINC5 incorporation into virions, providing a mechanism to explain how EnvCT truncation allows escape from restriction. Neutralization and inhibitor assays showed ΔCT viruses have an altered Env conformation and fusion kinetics, suggesting that EnvCT truncation dysregulates the processivity of entry, in turn allowing Env to escape targeting by SERINC5. Furthermore, HIV-1 and HIV-2 ΔCT viruses were also resistant to IFITMs, another entry-targeting family of restriction factors. Notably, while the EnvCT is essential for Env incorporation into HIV-1 virions and spreading infection in T cells, HIV-2 does not require the EnvCT. Here, we reveal a mechanism by which human lentiviruses can evade two potent Env-targeting restriction factors but show key differences in the capacity of HIV-1 and HIV-2 to exploit this. Taken together, this study provides insights into the interplay between HIV and entry-targeting restriction factors, revealing viral plasticity toward mechanisms of escape and a key role for the long lentiviral EnvCT in regulating these processes. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Env; HIV; IFITM; restriction; SERINC
语种	英语
scopus关键词	membrane protein; serine incorporator protein 3; serine incorporator protein 5; unclassified drug; differentiation antigen; isoprotein; leu-13 antigen; membrane protein; SERINC3 protein, human; SERINC5 protein, human; virus envelope protein; Article; controlled study; cytoplasm; cytoplasmic tail; genetic transfection; HEK293T cell line; HeLa cell line; human; human cell; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Lentivirus; nonhuman; virus cell interaction; virus entry; virus envelope; virus inhibition; virus mutant; virus neutralization; cell line; gene expression regulation; genetics; HEK293 cell line; Human immunodeficiency virus 1; Human immunodeficiency virus 2; Human immunodeficiency virus infection; immune evasion; immunology; pathogenicity; protein domain; signal transduction; stem cell; virion; virology; Antigens, Differentiation; Cell Line; env Gene Products, Human Immunodeficiency Virus; Gene Expression Regulation; HEK293 Cells; HeLa Cells; HIV Infections; HIV-1; HIV-2; Humans; Immune Evasion; Membrane Glycoproteins; Membrane Proteins; Protein Domains; Protein Isoforms; Signal Transduction; Stem Cells; Virion; Virus Internalization
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251168
作者单位	Division of Infection and Immunity, University College London, London, WC1E 6BT, United Kingdom
推荐引用方式 GB/T 7714	Haider T.,Snetkov X.,Jolly C.. HIV envelope tail truncation confers resistance to SERINC5 restriction[J],2021,118(21).
APA	Haider T.,Snetkov X.,&Jolly C..(2021).HIV envelope tail truncation confers resistance to SERINC5 restriction.Proceedings of the National Academy of Sciences of the United States of America,118(21).
MLA	Haider T.,et al."HIV envelope tail truncation confers resistance to SERINC5 restriction".Proceedings of the National Academy of Sciences of the United States of America 118.21(2021).